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TYK2-Wnt5a Crosstalk in Psoriatic Arthritis: A Hypothesized Immunopharmacological Axis for Inflammation and
Almeen Ansari1, Japneet Purewal Singh1, Gaurav Doshi2
1SVKM's Dr Bhanuben Nanavati College of Pharmacy, Mumbai, Pharmacology, India.
Introduction:
Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease marked by synovitis, enthesitis, bone erosion, and pathological new bone formation, via the Interleukin-23/T helper cell-17 (IL-23/Th17) axis. Tyrosine Kinase 2 (TYK2) mediates downstream signaling of IL-23, IL-12, and type I Interferons (IFN-I), whereas Wnt5a regulates non-canonical Wnt signaling in inflammation and skeletal remodelling. This review proposes and examines TYK2- Wnt5a crosstalk in PsA as a testable mechanistic hypothesis rather than an established pathway.
Methods:
A narrative literature search was conducted using PubMed, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov, combining terms 'TYK2', 'Wnt5a', 'Psoriatic arthritis', and 'Wnt/β-catenin'. Relevant peer-reviewed articles, clinical studies, and webpages published up to 2026 were evaluated with no lower date limit. Evidence on TYK2 signaling, Wnt5a-mediated pathways, PsA immunopathogenesis, bone remodelling, and TYK2-targeted therapies was critically synthesized in narrative form.
Results:
TYK2 drives Th17/Th1-mediated inflammation via IL-17 and IL-22, while Wnt5a promotes osteoclastogenesis and aberrant bone remodelling. Emerging evidence suggests that the TYK2- driven cytokine network may influence Wnt5a expression, creating a pathogenic link between chronic inflammation and structural damage. This proposed axis currently rests on parallel, circumstantial evidence rather than direct experimental demonstration that TYK2-dependent signaling regulates Wnt5a expression in PsA tissue and is treated throughout as a hypothesis requiring direct validation.
Discussion:
Understanding the TYK2-Wnt5a interaction could explain the coexistence of erosive and proliferative bone changes in PsA and may reveal combination or pathway-directed therapeutic strategies.
Conclusion:
The TYK2-Wnt5a axis is a promising, hypothesis-generating target in PsA; further mechanistic and clinical studies are needed to validate it therapeutically.
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